There are many technologies used commercially to select and screen compounds from large diverse protein libraries. These technologies include Phage Display, Ribosome Display, Yeast Display and Bacterial Display, in vitro compartmentalization, microengraving and spatial addressing. Lin et al., (2002). “Screening and Selection Methods for Large-Scale Analysis of Protein Function” Angew. Chem. Int. Ed., 41:4402-4425 (2002); Willats et al., (2002) “Phage display: practicalities and prospects” Plant Molecular Biology 50; 837-854; and Sergeeva et. al., (2006) “Display technologies: Applications for the discovery of drug and gene delivery agents” Advanced Drug Delivery Reviews 58:1622-1654.
The advent of phage display technology and alternative display systems allowed antibody screening by linking them to bacterial viruses and provided recovery of the antibody genes post screening by infection into bacteria. The technology has been widely commercialized. Due mainly to the costs of these licenses and the competitive nature of the lucrative antibody-based therapeutic market, alternative display technologies have also been developed. For example, microengraving microwells may capture single cells. Nonetheless, the current techniques lack the necessary robustness and selectivity to provide large-scale diagnostic and therapeutic screening.
A single-cell analysis in quantitative biology has been explored by various methods. Levsky et al., Science 297:836-840 2002; Hong et al., Nat. Biotechnol. 22:435-439 2004; Kurimoto et al., Nucleic Acids Res. 34:e42 (2006); Huang et al., Science 315:81-84 (2007); and Newman et al., Nature 441:840-846 (2006). However, these newly emerging methods have not been fully applied in the biological sciences as of yet. One of the reasons for this is the fact that these methods are too sophisticated and integrated to be used without appropriate investment of time, money, and labor. Thus, there is a strong need to simplify and make these methods more user-friendly for realization of quantitative biology at the single-cell level.
What is needed in the art is a better system for direct selection and characterization for processing cells and/or interacting biochemical pairs and selectively isolating each single cell.